Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000494368 | SCV000583207 | pathogenic | not provided | 2017-05-24 | criteria provided, single submitter | clinical testing | The c.2450delT variant in the ZFYVE26 gene has been previously reported in the heterozygous state in the presence of a second ZFYVE26 variant in an individual with cerebellar ataxia, axonal sensorimotor neuropathy, and generalized atrophy on brain MRI (Pyle et al., 2015). The c.2450delT variant causes a frameshift starting with codon Leucine 817, changes this amino acid to a Cysteine residue, and creates a premature Stop codon at position 12 of the new reading frame, denoted p.Leu817CysfsX12. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2450delT variant is not observed in the homozygous state, or at a significant frequency, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.2450delT as a pathogenic variant. |
Invitae | RCV001036170 | SCV001199521 | pathogenic | Spastic paraplegia | 2023-12-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu817Cysfs*12) in the ZFYVE26 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZFYVE26 are known to be pathogenic (PMID: 18394578, 19805727). This variant is present in population databases (rs768176054, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with a ZFYVE26-related condition (PMID: 25497598). ClinVar contains an entry for this variant (Variation ID: 430412). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Counsyl | RCV000664781 | SCV000788793 | likely pathogenic | Hereditary spastic paraplegia 15 | 2016-12-15 | no assertion criteria provided | clinical testing |